A straightforward access to trifluoromethylated natural products through late-stage functionalization

Covering: 2011 to 2021 Trifluoromethyl (CF3)-modified natural products have attracted increasing interest due to their magical effect in binding affinity and/or drug metabolism and pharmacokinetic properties. However, the chemo and regioselective construction of natural products (NPs) bearing a CF3 group still remains a long-standing challenge due to the complex chemical scaffolds and diverse reactive sites of NPs. In recent years, the development of late-stage functionalization strategies, including metal catalysis, organocatalysis, light-driven reactions, and electrochemical synthesis, has paved the way for direct trifluoromethylation process. In this review, we summarize the applications of these strategies in the late-stage trifluoromethylation of natural products in the past ten years with particular emphasis on the reaction model of each method. We also discuss the challenges, limitations, and future prospects of this approach.

Automated summary

This review summarizes the applications of late-stage functionalization strategies in the trifluoromethylation of natural products in the past ten years. These strategies include metal catalysis, organocatalysis, light-driven reactions, and electrochemical synthesis. The reaction models of each method are emphasized, along with the challenges, limitations, and future prospects of this approach.